Transcriptional activation of bovine mimecan by p53 through an intronic DNA-binding site

Mimecan is a small leucine-rich proteoglycan that can occur as either kerat an sulfate proteoglycan in the cornea or as glycoprotein in many connective tissues. As yet, there is no information on its transcriptional regulation . Recently we demonstrated the presence of eight mimecan mRNA transcripts g enerated by alternative transcription initiation, alternative polyadenylati on. and differential splicing, all of which encode an identical protein. He re we report a conserved consensus p53-binding DNA sequence in the first in tron of bovine and human mimecan genes and show that wild-type p53 binds to this sequence in vitro. Co-transfections of Saos-2, HeLa. NIH 3T3, and pri mary bovine corneal keratocytes with bovine mimecan promoter/luciferase rep orter constructs in combination with p53 expression vectors activate the se cond mimecan promoter through the p53- binding sequence. In addition, we sh ow absence of mimecan expression in different tumors and cancer cell lines, where p53 frequently is inactivated/mutated. Thus. this work provides nove l information that links mimecan to the p53 network. (C) 2001 Elsevier Scie nce B.V. All rights reserved.